What is the relationship between Hepatitis C (HCV) and vasculitis?

From the Guidelines

Hepatitis C virus (HCV) infection is strongly associated with the development of vasculitis, particularly cryoglobulinemic vasculitis, which can be effectively managed by treating the underlying HCV infection with direct-acting antiviral (DAA) therapy. The relationship between HCV and vasculitis is well-established, with HCV infection triggering the production of immune complexes that deposit in blood vessel walls, leading to inflammation and damage 1. The most common form of vasculitis associated with HCV is cryoglobulinemic vasculitis, which typically affects small and medium-sized blood vessels and presents with symptoms like skin rashes, joint pain, nerve damage, and kidney problems.

Key Findings

• A prospective international multicentre cohort study found that DAA therapy induced a complete clinical response in 73% of patients with cryoglobulin-associated vasculitis 1.
• Symptoms of purpura were cleared from 97% of patients, renal involvement from 91% of patients, arthralgias from 86% of patients, and neuropathy from 77% of patients 1.
• Cryoglobulins were no longer detected in 53% of patients after DAA therapy 1.

Treatment Approach

• Treating the underlying HCV infection with DAA therapy is crucial in managing vasculitis symptoms, with cure rates exceeding 95% 1.
• Additional immunosuppressive therapy, such as rituximab, corticosteroids, or plasmapheresis, may be needed for severe vasculitis manifestations 1.
• DAA therapy regimens, such as sofosbuvir/velpatasvir (Epclusa), glecaprevir/pibrentasvir (Mavyret), or sofosbuvir/ledipasvir (Harvoni), are typically given for 8-12 weeks depending on the specific regimen and patient factors.

From the Research

Relationship between Hepatitis C (HCV) and Vasculitis

• Hepatitis C infection is often associated with extrahepatic manifestations, including cryoglobulinemic vasculitis 2.
• Cryoglobulinemic vasculitis is a small-vessel systemic vasculitis that results from the circulation and precipitation of cryoglobulins and complement activation 3.
• The disease expression of mixed cryoglobulinemia vasculitis is variable, ranging from mild clinical symptoms to fulminant life-threatening complications 4.

Treatment of HCV-Associated Vasculitis

• Antiviral therapy, such as Peg-IFNalpha and ribavirin, is often used as induction therapy for HCV-associated mixed cryoglobulinemia vasculitis with mild to moderate disease severity and activity 4.
• Combination therapy with rituximab and Peg-IFNalpha plus ribavirin may be effective in targeting both the viral trigger and cryoglobulin-producing B-cells 2, 4.
• Direct-acting antivirals (DAA) have drastically changed chronic HCV therapy and have been shown to improve extrahepatic manifestations such as cryoglobulinemia vasculitis 5, 3.
• DAA therapy has been associated with high sustained virological response (SVR) rates and improvement in clinical symptoms, including cutaneous, articular, neurologic, and renal manifestations 5, 3.

Efficacy of Rituximab in HCV-Associated Vasculitis

• Rituximab has been shown to be effective in managing HCV-associated cryoglobulinemic vasculitis, either alone or with antiviral therapy 2, 6.
• The use of rituximab may slightly improve skin vasculitis and make little or no difference to kidney disease 6.
• Rituximab may also increase infusion reactions compared to immunosuppressive medication, but discontinuations of treatment due to adverse reactions are similar 6.